Incidence of Thrombotic Complications with Use of Peg-Asparginase in Treatment for Acute Lymphoblastic Leukemia (ALL) in Adults and Young Adolescent Patients

Introduction: Peg-Asparginase is routinely used in the chemotherapy regimens used for treatment of ALL. Incidence of thrombotic complications is well established in children but there is limited data in adult and young adolescent patients. This is retrospective analysis to assess the risk of thrombotic complications with use of Peg-Asparginase.

Methods and Results: 100 patients with Acute Lymphoblastic Leukaemia treated between 2007-2015 who received Peg-Asparginase containing chemotherapy regimen were evaluated for development of thrombotic complications and pancreatitis. There were 69 male patients and 31 female patients. Median age was 29 yr. (range: 16-68 yr). Route of administration for Peg-Asparginase was intravenous in 51 cases and intramuscular in 49 cases. Peg-Aspraginase was administered during induction phase and consolidation cycles according to the relevant chemotherapy protocols. The adverse events included deep vein thrombosis (DVT) in 15 (15%), cerebral venous thrombosis in 7 (7%), Pancreatitis in 2 (2%), DVT and pancreatitis in 1 (1%) and 1 patient had clinically suspected DVT (1%). Complication rate was similar with IV or IM route of administration. 10 patients in IM group (20.4%) and 17 patients in IV group (33.3%) had at least one complication with Peg-Asparginase (P=0.31). Risk of individual complications was similar in both groups (DVT: 14.3% vs. 21.6%, p=0.34; Pancreatitis 2% vs. 3.9%, p=0.57; Cerebral venous thrombosis 4%% vs. 9.8%, p=0.25). There was no difference in the incidence of thrombotic complications with gender, age at diagnosis and use of central venous lines.

Conclusions: There is a significant risk of thrombotic events including PE (18% risk of thrombotic events excluding CNS). Risk of CNS events is 7% in this population. Risk appears to be higher with IV administration but this is not statistically significant due to small sample size. Incidence of CNS events is similar to that reported in adolescents participating in UKALL2003 study. The analysis will be extended to evaluate other toxicities especially hepatic toxicity and identify if there are any high risk patients for CNS or thrombotic events including blood counts, clotting, and cytogenetics. Use of LMWH prophylaxis seems reasonable in view of high incidence of thrombotic events even if CNS events are excluded.